Travel Surveillance and Genomics Uncover a Hidden Zika Outbreak during the Waning Epidemic

Summary The Zika epidemic in the Americas has challenged surveillance and control. As the epidemic appears to be waning, it is unclear whether transmission is still ongoing, which is exacerbated by discrepancies in reporting. To uncover locations with lingering outbreaks, we investigated travel-associated Zika cases to identify transmission not captured by reporting. We uncovered an unreported outbreak in Cuba during 2017, a year after peak transmission in neighboring islands. By sequencing Zika virus, we show that the establishment of the virus was delayed by a year and that the ensuing outbreak was sparked by long-lived lineages of Zika virus from other Caribbean islands. Our data suggest that, although mosquito control in Cuba may initially have been effective at mitigating Zika virus transmission, such measures need to be maintained to be effective. Our study highlights how Zika virus may still be “silently” spreading and provides a framework for understanding outbreak dynamics. Video Abstract

[1]  I. Yoon,et al.  An Update on Zika Virus in Asia , 2017, Infection & chemotherapy.

[2]  N. R. Faria,et al.  Establishment and cryptic transmission of Zika virus in Brazil and the Americas , 2017, Nature.

[3]  Simon Cauchemez,et al.  Edinburgh Research Explorer Middle East respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility , 2022 .

[4]  M. Boelaert,et al.  Towards active community participation in dengue vector control: results from action research in Santiago de Cuba, Cuba. , 2007, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[5]  V. Colizza,et al.  Local and regional spread of chikungunya fever in the Americas. , 2014, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[6]  M. Kraemer,et al.  Inferring the risk factors behind the geographical spread and transmission of Zika in the Americas , 2018, PLoS neglected tropical diseases.

[7]  E. Lyons,et al.  Pandemic Potential of a Strain of Influenza A (H1N1): Early Findings , 2009, Science.

[8]  M. Suchard,et al.  Air Travel Is Associated with Intracontinental Spread of Dengue Virus Serotypes 1–3 in Brazil , 2014, PLoS neglected tropical diseases.

[9]  N. Low,et al.  How Relevant Is Sexual Transmission of Zika Virus? , 2016, PLoS medicine.

[10]  Karthik Gangavarapu,et al.  An amplicon-based sequencing framework for accurately measuring intrahost virus diversity using PrimalSeq and iVar , 2018, Genome Biology.

[11]  Andrew Rambaut,et al.  Exploring the temporal structure of heterochronous sequences using TempEst (formerly Path-O-Gen) , 2016, Virus evolution.

[12]  Peter J. A. Cock,et al.  Bio.Phylo: A unified toolkit for processing, analyzing and visualizing phylogenetic trees in Biopython , 2012, BMC Bioinformatics.

[13]  A. Fauci,et al.  Pandemic Zika: A Formidable Challenge to Medicine and Public Health , 2017, The Journal of infectious diseases.

[14]  FOURTH MEETING OF THE EMERGENCY COMMITTEE UNDER THE INTERNATIONAL HEALTH REGULATIONS (2005) REGARDING MICROCEPHALY, OTHER NEUROLOGICAL DISORDERS AND ZIKA VIRUS , 2016, Saudi Medical Journal.

[15]  D. Cummings,et al.  Long-term circulation of Zika virus in Thailand: an observational study. , 2019, The Lancet. Infectious diseases.

[16]  Ziheng Yang Maximum likelihood phylogenetic estimation from DNA sequences with variable rates over sites: Approximate methods , 1994, Journal of Molecular Evolution.

[17]  Samuel S. C. Rund,et al.  Rescuing Troves of Data to Tackle Emerging Mosquito-Borne Diseases , 2017, bioRxiv.

[18]  M. Castro,et al.  Congenital Zika virus syndrome in Brazil: a case series of the first 1501 livebirths with complete investigation , 2016, The Lancet.

[19]  J. B. P. Lima,et al.  Evidence of vertical transmission of Zika virus in field-collected eggs of Aedes aegypti in the Brazilian Amazon , 2018, PLoS neglected tropical diseases.

[20]  Jessica Patterson,et al.  Dengue, Zika and Chikungunya: Emerging Arboviruses in the New World , 2016, The western journal of emergency medicine.

[21]  G. Chowell,et al.  Prior dengue virus infection and risk of Zika: A pediatric cohort in Nicaragua , 2019, PLoS medicine.

[22]  Eli Schwartz,et al.  Seasonality, Annual Trends, and Characteristics of Dengue among Ill Returned Travelers, 1997–2006 , 2008, Emerging infectious diseases.

[23]  Samuel S. C. Rund,et al.  Rescuing Troves of Hidden Ecological Data to Tackle Emerging Mosquito-Borne Diseases. , 2019, Journal of the American Mosquito Control Association.

[24]  M. Kraemer,et al.  Emergence of the Zika virus Asian lineage in Angola , 2019, bioRxiv.

[25]  O. Brady,et al.  High Zika Virus Seroprevalence in Salvador, Northeastern Brazil Limits the Potential for Further Outbreaks , 2017, mBio.

[26]  S. Cauchemez,et al.  Reassessing Serosurvey-Based Estimates of the Symptomatic Proportion of Zika Virus Infections , 2018, American journal of epidemiology.

[27]  T. Frieden,et al.  Public health in Haiti--challenges and progress. , 2011, The New England journal of medicine.

[28]  Alexandros Stamatakis,et al.  RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies , 2014, Bioinform..

[29]  P. Lemey,et al.  Tracking virus outbreaks in the twenty-first century , 2018, Nature Microbiology.

[30]  Chui Rhong. Chang,et al.  Zika in travellers 1947-2017: a systematic review. , 2018, Journal of travel medicine.

[31]  Brian F. Havel,et al.  International Air Transport Association , 2010 .

[32]  Richard Durbin,et al.  Sequence analysis Fast and accurate short read alignment with Burrows – Wheeler transform , 2009 .

[33]  Kay Hailbronner,et al.  INTERNATIONAL AIR TRANSPORT ASSOCIATION , 1983 .

[34]  Marko Kolenc,et al.  Zika Virus Associated with Microcephaly. , 2016, The New England journal of medicine.

[35]  Daniel L. Ayres,et al.  Bayesian phylogenetic and phylodynamic data integration using BEAST 1.10 , 2018, Virus evolution.

[36]  K. Leder,et al.  Zika beyond the Americas: Travelers as sentinels of Zika virus transmission. A GeoSentinel analysis, 2012 to 2016. , 2017, PloS one.

[37]  O. Gascuel,et al.  A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. , 2003, Systematic biology.

[38]  Leah R Johnson,et al.  Detecting the impact of temperature on transmission of Zika, dengue, and chikungunya using mechanistic models , 2017, PLoS neglected tropical diseases.

[39]  Mary E. Wilson,et al.  GeoSentinel Surveillance of Illness in Returned Travelers, 2007–2011 , 2013, Annals of Internal Medicine.

[40]  Oliver G. Pybus,et al.  Precision epidemiology for infectious disease control , 2019, Nature Medicine.

[41]  S. Ho,et al.  Relaxed Phylogenetics and Dating with Confidence , 2006, PLoS biology.

[42]  O. Brady,et al.  Projecting the end of the Zika virus epidemic in Latin America: a modelling analysis , 2018, bioRxiv.

[43]  S. Weaver,et al.  Zika, Chikungunya, and Other Emerging Vector-Borne Viral Diseases. , 2018, Annual review of medicine.

[44]  M. Cetron,et al.  Assessing the Origin of and Potential for International Spread of Chikungunya Virus from the Caribbean , 2014, PLoS currents.

[45]  P. Brasil,et al.  Accuracy of Zika virus disease case definition during simultaneous Dengue and Chikungunya epidemics , 2017, PloS one.

[46]  G. Ebel,et al.  Arbovirus coinfection and co-transmission: A neglected public health concern? , 2019, PLoS biology.

[47]  Shane S. Sturrock,et al.  Geneious Basic: An integrated and extendable desktop software platform for the organization and analysis of sequence data , 2012, Bioinform..

[48]  D. Musso,et al.  Emergence of Zika Virus , 2015 .

[49]  Eduardo Massad,et al.  DengueTools: innovative tools and strategies for the surveillance and control of dengue , 2012, Global health action.

[50]  S. Reardon Mosquito guns and heavy fines: how Cuba kept Zika at bay for so long , 2016, Nature.

[51]  D. Gubler,et al.  Aedes aegypti and Aedes aegypti-borne disease control in the 1990s: top down or bottom up. Charles Franklin Craig Lecture. , 1989, The American journal of tropical medicine and hygiene.

[52]  O. Pybus,et al.  Epidemiology of the Zika Virus Outbreak in the Cabo Verde Islands, West Africa , 2018, PLoS currents.

[53]  Daniel L. Ayres,et al.  BEAGLE: An Application Programming Interface and High-Performance Computing Library for Statistical Phylogenetics , 2011, Systematic biology.

[54]  Karthik Gangavarapu,et al.  Genome sequencing reveals Zika virus diversity and spread in the Americas , 2017, bioRxiv.

[55]  M. Guzmán Deciphering Dengue: The Cuban Experience , 2005, Science.

[56]  Trevor Bedford,et al.  Multiplex PCR method for MinION and Illumina sequencing of Zika and other virus genomes directly from clinical samples , 2017, Nature Protocols.

[57]  Pratibha Sharma,et al.  Zika virus outbreak in Rajasthan, India in 2018 was caused by a virus endemic to Asia. , 2019, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[58]  A. LaBeaud Why Arboviruses Can Be Neglected Tropical Diseases , 2008, PLoS neglected tropical diseases.

[59]  John D. Hunter,et al.  Matplotlib: A 2D Graphics Environment , 2007, Computing in Science & Engineering.

[60]  J. E. Muñoz-Medina,et al.  Genomic Epidemiology Reconstructs the Introduction and Spread of Zika Virus in Central America and Mexico , 2018, Cell host & microbe.

[61]  David L. Smith,et al.  The global distribution of the arbovirus vectors Aedes aegypti and Ae. albopictus , 2015, eLife.

[62]  K. Katoh,et al.  MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability , 2013, Molecular biology and evolution.

[63]  Jonathan E. Suk,et al.  International Dispersal of Dengue through Air Travel: Importation Risk for Europe , 2014, PLoS neglected tropical diseases.

[64]  E. Mendelson,et al.  Zika Virus Disease in Traveler Returning from Vietnam to Israel , 2016, Emerging infectious diseases.

[65]  Nuno R. Faria,et al.  Epidemiology of the Zika virus outbreak in the Cabo Verde Islands, West Africa , 2018 .

[66]  Marli Tenório Cordeiro,et al.  Seroprevalence and risk factors for dengue infection in socio-economically distinct areas of Recife, Brazil. , 2010, Acta tropica.

[67]  H. Guzmán,et al.  Vertical Transmission of Zika Virus in Aedes aegypti Mosquitoes , 2016, The American journal of tropical medicine and hygiene.

[68]  C. Jessica E. Metcalf,et al.  Assessing the global threat from Zika virus , 2016, Science.

[69]  Madison,et al.  Surveillance for travel-related disease--GeoSentinel Surveillance System, United States, 1997-2011. , 2013, Morbidity and mortality weekly report. Surveillance summaries.

[70]  D. Cummings,et al.  Impact of preexisting dengue immunity on Zika virus emergence in a dengue endemic region , 2019, Science.

[71]  Joanne Turner,et al.  Global risk model for vector-borne transmission of Zika virus reveals the role of El Niño 2015 , 2016, Proceedings of the National Academy of Sciences.

[72]  S. Hay,et al.  Zika virus transmission in Angola and the potential for further spread to other African settings , 2017, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[73]  O. Pybus,et al.  Genomic Insights into Zika Virus Emergence and Spread , 2018, Cell.

[74]  O. Brady,et al.  Potential Zika virus spread within and beyond India. , 2018, Journal of travel medicine.

[75]  S. Wacharapluesadee,et al.  Molecular Epidemiology and Genetic Diversity of Zika Virus from Field-Caught Mosquitoes in Various Regions of Thailand , 2019, Pathogens.

[76]  Hayden C. Metsky,et al.  Genomic epidemiology reveals multiple introductions of Zika virus into the United States , 2017, Nature.

[77]  M. Cetron,et al.  Travel-Associated Zika Virus Disease Acquired in the Americas Through February 2016: A GeoSentinel Analysis. , 2016, Annals of internal medicine.

[78]  J. H. Huber,et al.  Temperature modulates dengue virus epidemic growth rates through its effects on reproduction numbers and generation intervals , 2017, PLoS neglected tropical diseases.

[79]  G. Pugliese,et al.  Severe Streptococcus pyogenes Infections, United Kingdom, 2003–2004 , 2008, Emerging infectious diseases.

[80]  John S Brownstein,et al.  Potential for Zika virus introduction and transmission in resource-limited countries in Africa and the Asia-Pacific region: a modelling study. , 2016, The Lancet. Infectious diseases.

[81]  Mevin B. Hooten,et al.  Bayesian Models: A Statistical Primer for Ecologists , 2015 .

[82]  Mandev S. Gill,et al.  Improving Bayesian population dynamics inference: a coalescent-based model for multiple loci. , 2013, Molecular biology and evolution.

[83]  A. L. Mosimann,et al.  First report of autochthonous transmission of Zika virus in Brazil , 2015, Memorias do Instituto Oswaldo Cruz.

[84]  E. Harris,et al.  Seroprevalence, risk factor, and spatial analyses of Zika virus infection after the 2016 epidemic in Managua, Nicaragua , 2018, Proceedings of the National Academy of Sciences.

[85]  P. Hotez Neglected Tropical Diseases in the Anthropocene: The Cases of Zika, Ebola, and Other Infections , 2016, PLoS neglected tropical diseases.